同源盒转录因子CDX2与Y染色体决定因子SOX9在肠上皮化生及胃癌组织中的表达

摘要

目的:研究同源盒转录因子CDX2和Y染色体决定因子SOX9在肠上皮化生(intestinal metaplasia,IM)及胃癌组织中的表达,探讨CDX2和SOX9在IM发生、进展及胃癌发生、发展中的作用及相互关系.方法:选取慢性萎缩性胃炎(chronic atrophic gastritis,CAG)伴IM 24例、癌旁IM 17例、胃癌组织50例,用HE染色对IM及胃癌进行组织学分型,免疫组化法观察CDX2、SOX9蛋白在上述各种胃黏膜组织中的表达,研究二者表达与胃癌临床病理学特征之间的关系.结果:CDX2蛋白表达阳性率在CAG伴IM组、癌旁IM组和胃癌组分别为87.50％、76.47％和62.00％,CAG伴IM组显著高于胃癌组(P＜0.05),CAG伴IM组与癌旁IM组、癌旁IM组与胃癌组之间比较无统计学差异(P＞0.05),肠型胃癌显著高于弥漫型胃癌(77.78％ vs 43.48％,P=0.013).CDX2蛋白在胃癌中的表达与胃癌临床分期、分化程度、Lauren分型及是否有浆膜浸润等有关.SOX9蛋白表达阳性率,在CAG伴IM组、癌旁IM组及胃癌组分别为54.17％、70.59％、80.00％,CAG伴IM组显著低于胃癌组(P＜0.05),CAG伴IM组与癌旁IM组、癌旁IM组与胃癌组之间比较无统计学差异(P＞0.05),肠型胃癌显著高于弥漫型胃癌(92.59％ vs 65.22％,P=0.040).SOX9蛋白在胃癌中的表达与胃癌分化程度、临床分期、Lauren分型和是否淋巴结转移等有关联.胃癌组织中CDX2和SOX9的阳性表达存在显著性负相关(r=-0.391,X2=5.778,P=0.016).结论:CDX2、SOX9在IM及肠型胃癌的发生中可能有重要作用,可做为IM及肠型胃癌预测的特异性指标之一.二者可能在胃癌进展及浸润转移过程中起重要作用,联合检测对选择合适治疗方式及预后判断具有重要价值.%Objective:To study the expressions of CDX2 and SOX9 protein in intestinal metaplasia (IM) and gastric cancer tissue,and to investigate the roles of CDX2 and SOX9 in the development of IM and gastric carcinogenesis and progression.Methods:24 cases of chronic atrophic gastritis (CAG) with IM,17 cases of paracancerous IM and 50 cases of gastric cancer were selected to the study.HE staining was used to classify IM and gastric cancer,and the expressions of CDX2 and SOX9 protein in different gastric lesions were assessed with immunohistochemistry SP method.The relationships between CDX2,SOX9 expressions and gastric cancer clinical-pathologic significance were analyzed in all gastric cancer patients.Results:CDX2 protein expressional positive rates in CAG with IM group,paracancerous IM group and gastric cancer group were 87.50％,76.47％ and 62.00％ respectively.CAG with IM group was significant lower than in the gastric cancer group (P ＜ 0.05),and there were no significant differences between CAG with IM group and paracancerous IM group,the same as that between paracancerous IM group and gastric cancer group.The intestinal-type gastric cancer was significant higher than the diffuse-type gastric cancer (77.78％ vs 43.48％,P =0.013).The expression of CDX2 in gastric cancer was significant associated with tumor TNM staging,differentiation,Lauren classification and the depth of tumor infiltration (P ＜ 0.05).SOX9 protein expressional positive rates in CAG with IM group,paracancerous IM group and gastric cancer group were 54.17％,70.59％ and 80.00％ respectively.CAG with IM group was significant lower than in gastric cancer group (P ＜ 0.05).There were no significant differences between CAG with IM group and paracancerous IM group,the same as that between paracancerous IM group and gastric cancer group.The intestinal-type gastric cancer was significant higher than the diffuse-type gastric cancer (92.59％ vs 65.22％,P =0.040).The expression of SOX9 in gastric cancer was significantly associated with tumor differentiation,TNM staging,Lauren classification and lymph nodes metastasis (P ＜ 0.05).The positive expressions of CDX2 were negatively correlated with that of SOX9 in gastric cancer (r=-0.391,x2 =5.778,P =0.016).Conclusion:CDX2 and SOX9 may play important roles in the development,progression of IM and gastric carcinogenesis,and probably can be used as a specific predictive index for IM and intestinal-type gastric cancer.CDX2 and SOX9 may also play important roles in the progression,infiltration,metastasis of gastric cancer,and combined dectection of the two factors may serve as valuable markers to selecte suitable therepy method and evaluate the prognosis of gastric cancer.